Addition of Paclitaxel to Primary Systemic Therapy Doubles the Chance of Avoiding Mastectomy

The addition of paclitaxel(Drug information on paclitaxel) before surgery to primary systemic therapy with doxorubicin(Drug information on doxorubicin), followed by CMF (cyclophosphamide [Cytoxan, Neosar], methotrexate(Drug information on methotrexate), fluorouracil(Drug information on fluorouracil)) has significant antitumor effects, according to the preliminary results of the European Cooperative Trial in Operable Breast Cancer (ECTO) study. In the neoadjuvant arm, 52% of patients with tumors larger than 2 cm had a complete clinical response and an additional 29% had a partial response. The high antitumor activity led to a reduction in the need for mastectomy and allowed for the performance of more conservative breast surgery (68%) than in the adjuvant treatment group (34%).

Dramatic Downstaging

A clear benefit in terms of pathologic complete response was seen in 22% of patients and associated with negative axillary nodes in 89% of these patients. Dr. Luca Gianni, director, division of Medical Oncology A, Istituto Nazionale Tumori, Milan, Italy, and chairman of the ECTO study said, "The extent of downstaging with primary systemic therapy with doxorubicin and paclitaxel followed by CMF was dramatic. Treatment was effective both at the primary tumor and the axillary metastases, and this led to a significant increase in the frequency of conservative surgery compared with conventional treatment."

For the study, patients with operable breast cancer (tumor > 2 cm) were randomized to one of the following treatment strategies: (1) adjuvant therapy with sequential doxorubicin followed by CMF, (2) adjuvant therapy with sequential doxorubicin and paclitaxel followed by CMF, or (3) primary systemic therapy (doxorubicin and paclitaxel followed by CMF). The trial investigated whether sequential chemotherapy for eight cycles prior to surgery would provide a benefit compared with the usual approach of administering adjuvant therapy after surgery and whether the addition of paclitaxel would provide further benefits compared to non-paclitaxel-based chemotherapy.

Tolerable Side-Effect Profile

Treatment with paclitaxel in combination with doxorubicin and followed by CMF was well tolerated. The incidence of side effects was similar to that seen in patients treated with conventional therapy. Treatment rarely caused febrile neutropenia or grade 3 neurotoxicity, and there was no evidence of any relevant increase in cardiotoxicity with the addition of paclitaxel to doxorubicin, either as primary systemic therapy or adjuvant therapy.

"Primary systemic therapy provided a very good way of testing directly the sensitivity of individual tumors to specific therapies and will improve our ability to tailor treatments to specific needs of the patient," Dr. Gianni concluded. "The preliminary results of this study show that the combination of paclitaxel and doxorubicin followed by CMF as neoadjuvant therapy has significant beneficial effects on locoregional tumor control. As of today, we can only say that this translates as significant improvement in the frequency of conservative breast surgery."

He added, "Paclitaxel is currently used to treat metastatic breast cancer, but this study suggests that earlier use of paclitaxel in breast cancer can confer benefits seen so far in the ECTO study. These preliminary results are encouraging. In another 2 to 3 years time, survival data will tell us whether the addition of paclitaxel also provides long-term benefit."